Proteomic analysis of the effect of iptakalim on human pulmonary arterial smooth muscle cell proliferation

AIM: To investigate the anti-proliferative effect of iptakalim (Ipt), a newly selective K(ATP) channel opener, in endothelin-1 (ET-1)-induced human pulmonary arterial smooth muscle cells (PASMCs) using proteomic analysis.

METHODS: Human PASMCs were incubated with ET-1 (10(-8) mol/L) and ET-1 (10(-8) mol/L) plus iptaklim (10(-5) mol/L) for 24 h. Analysis via 2-DE gel electrophoresis and MALDI-TOF-MS was employed to display the different protein profiles of whole-cell protein from cultures of control, ET-1 treatment alone, and treatment with ET-1 and iptaklim combined. Real time RT-PCR and Western blot analysis were used to confirm the proteomic analysis.

RESULTS: When iptakalim inhibited the proliferative effect of ET-1 in human PASMCs by opening the K(ATP) channels, the expression of different groups of cellular proteins was changed, including cytoskeleton-associated proteins, plasma membrane proteins and receptors, chaperone proteins, ion transport-associated proteins, and glycolytic and metabolism-associated proteins. We found that iptakalim could inhibit the proliferation of human PASMCs partly by affecting the expression of Hsp60, vimentin, nucleoporin P54 (NUP54) and Bcl-X(L) by opening the K(ATP) channel.

CONCLUSION: The data suggest that a wide range of signaling pathways may be involved in abolishing ET-1-induced proliferation of human PASMCs following iptakalim treatment.

Medienart:

E-Artikel

Erscheinungsjahr:

2009

Erschienen:

2009

Enthalten in:

Zur Gesamtaufnahme - volume:30

Enthalten in:

Acta pharmacologica Sinica - 30(2009), 2 vom: 19. Feb., Seite 175-83

Sprache:

Englisch

Beteiligte Personen:

Yang, Ming-Xia [VerfasserIn]
Liu, Zheng-Xia [VerfasserIn]
Zhang, Shu [VerfasserIn]
Jing, Yu [VerfasserIn]
Zhang, Shi-Jiang [VerfasserIn]
Xie, Wei-Ping [VerfasserIn]
Ma, Lei [VerfasserIn]
Zhu, Chang-Liang [VerfasserIn]
Wang, Hong [VerfasserIn]

Links:

Volltext

Themen:

Endothelin-1
Journal Article
N-(1-methylethyl)-1,1,2-trimethylpropylamine
Propylamines
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 28.04.2009

Date Revised 20.10.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1038/aps.2008.30

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM185986145